Neurokinin-3 Receptor Antagonist Intermediate Synthesis Without Toxic Reagents
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Solution Overview
Problem
Existing synthetic methods for neurokinin-3-receptor agonists, such as Fezolinetant, involve the use of toxic and hazardous reagents like carbon monoxide and hydrazine, making them unsuitable for industrial-scale production, and require protecting and deprotecting steps that complicate the process.
Innovation Solution
A process involving the reaction of a compound of formula XIII with a compound of formula XIV in the presence of metal-based catalysts, ligands, and bases in suitable solvents to produce compounds of formula X, avoiding the use of intermediates like thiazolecarbohydrazide IX, thereby eliminating the need for toxic reagents and simplifying the synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing synthetic methods using carbon monoxide and hydrazine are employed, then the synthesis of neurokinin-3-receptor agonists can be achieved, but the process becomes hazardous and unsuitable for industrial-scale production
Solution Approach 1:
The patent removes the hazardous reagents (carbon monoxide and hydrazine) from the synthetic pathway by employing alternative reaction conditions that achieve the same chemical transformation without requiring these toxic substances, thereby eliminating the associated safety hazards for industrial production
Solution Approach 2:
The patent transforms a potentially harmful process into a safe one by replacing toxic reagents with safer alternatives, converting the harmful synthetic route into a beneficial industrial process that maintains effectiveness while eliminating toxicity
2Manufacturing precision
If protecting and deprotecting steps are included in the synthesis, then the desired compounds can be obtained, but the process complexity increases
Solution Approach 1:
The patent extracts and eliminates the unnecessary protecting and deprotecting steps from the synthetic pathway, achieving direct transformation of the starting materials into the desired compounds without requiring intermediate protection of functional groups
Solution Approach 2:
The patent employs reaction conditions that are selective enough to achieve the desired transformation without requiring preliminary protection of other functional groups, allowing the synthesis to proceed directly to the target compound
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method provides a safer and scalable synthesis of neurokinin-3-receptor agonists, such as Fezolinetant, by eliminating the use of toxic reagents and reducing the complexity of the manufacturing process.
Implementation Method 1
reacting a compound of formula XIII with a compound of formula XIV in a suitable solvent in the presence of one or more metal-based catalysts
Data Source
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AI summary
The present invention relates to synthetic processes for the preparation of compounds having activity as neurokinin-3-receptor agonists, among which Fezolinetant, and of intermediates useful in the synthesis thereof.